The present invention relates to new synthetic intermediates useful for producing ticlopidine hydrochloride having an effect of inhibiting platelet aggregation in an economical manner on an industrial scale, and a process for producing them.
Reports were made from old times on the synthesis of a 4,5,6,7-tetrahydrothieno[3,2-c]pyridine skeleton of ticlopidine hydrochloride. The processes for the synthesis can be roughly divided into two processes. One is a process wherein a thiophene derivative is used as the starting material and a tetrahydropyridine ring is closed [see, for example, Japanese Patent Publication for Opposition Purpose (hereinafter referred to as "J.P. KOKOKU") No. Sho 56-2068, Japanese Patent Unexamined Published Application (hereinafter referred to as "J.P. KOKAI") No. Sho 62-103088 and EP 439404A2] and the other is a process wherein a piperidone derivative is used as the starting material and a thiophene ring is closed (see, for example, J.P. KOKAI Nos. Sho 63-2992 and Sho 63-I26883, EP 360293A2 and DE 2,701,511). The reaction schemes of them are as follows: ##STR3##
The known reaction schemes 1, 2 and 3 are disclosed in J.P. KOKAI No. Sho 62-103088, EP 360293A2 and J.P. KOKAI No. 63-2992, respectively. Although the known reaction scheme 1 comprising only a small number of the reaction steps is an advantageous process, a further improvement is demanded, since it has problems that a cyanide is used as the starting material and that side reactions occur in the course of the reduction. The investigations of the known reaction schemes 2 and 3 were started relatively recently and only a very small number of reports were proposed. Thus no process for producing the intended compound from an inexpensive starting material by short steps has been found yet.